The excretory function of the kidney, the formation of urine, begins in the kidney with filtration of blood at the glomerulus which is a tuft of capillaries. These capillaries invaginate a surrounding capsule called Bowman's capsule where the renal tubule system begins. The structure of the glomerulus is designed to provide efficient ultrafiltration of blood to remove toxic wastes from the circulation and retain important components within the systemic circulation, such as albumin (see, e.g., Brenner and Humes, New Engl. J. Med. 297:148-154, 1977; Brenner et al., New Engl. J. Med. 298:826-833, 1978; both incorporated herein by reference in their entireties).
The regulatory function of the kidney, especially with regard to fluid and electrolyte homeostasis, is provided by the tubular segments attached to the glomerulus. It is in the renal tubules where processes of osmosis, diffusion as well as active transport all assist in converting glomerular filtrate into urine. The ultrafiltrate emanating from the glomerulus courses along the kidney tubule which reabsorbs fluid and solutes to finely regulate the excretion of various amounts of solutes and water in the final urine. The functional unit of the kidney is, therefore, composed of the filtering unit, the glomerulus, and the regulatory unit, the tubule. Together they form the basic component of the kidney, called the nephron.
End stage renal disorder (ESRD) is a common clinical syndrome involving a decline in renal function, either acutely or chronically. The clinical manifestations of this disorder arise from a decrease in the glomerular filtration rate and an inability of the kidney to excrete the toxic metabolic wastes produced by the body. The complete treatment of ESRD is dependent upon the replacement of the filtrative, reabsorptive, homeostatic and endocrine functions of the kidney as an integrated organ structure.
Hemodialysis and chronic ambulatory peritoneal dialysis (CAPD) involves long-term ex vivo replacement therapy for support of renal function (see, e.g., Iglehart, N. Engl. J. Med. 328:366-371, 1993; Excerpts from United States Renal Data System 1991 Annual Data Report. Am. J. Kidney Diseases 18(5) Supplement 2:21-30, November, 1991; herein incorporated by reference in its entirety). Conventional hemodialysis for ESRD mimics to some extent the filtration function of the kidney by circulating a patient's blood through or over a dialysate solution physically separated from the blood by a porous or permeable wall or membrane. The process results in the preferential diffusion of small molecules, such as urea, from the bloodstream into the dialysate solution. Examples of some hemodialyzers and their function are described, for example, in U.S. Pat. Nos. 3,370,710; 3,373,876; 3,505.686; 3,704,223; 3,864,259; 3,884,808; 4,176,069 and 4,354,933; each herein incorporated herein by reference in their entireties.
Although hemodialysis adequately removes small molecules from the bloodstream, no method has been established which provides for selectively removing or retaining larger molecules. Furthermore, dialysate solutions must be carefully controlled to ensure that their concentrations of biologically essential materials (such as inorganic salts and glucose) are balanced so that these materials which are present in the blood are retained by the blood. There is a strong need for improvements over existing systems.
Organ transplantation is also a limited therapeutic option due to the lack of available organs, the obligatory immunosuppressant medication that must be taken, and the high risk for tissue rejection.
What are needed are viable alternatives to dialysis and organ transplantation for treating kidney failure and kidney disease. In particular, artificial devices the mimic one or more functions of kidneys are needed that are configured for implantation into a patient. Ideally, such devices are configured for extended placement in the patient.